The present invention is directed to materials for neutralization of chemical and biological compounds or agents, and especially chemical and biological weapons agents and their method of making. In particular, the present invention is directed to materials containing solubilizing compounds and reactive compounds that can be delivered as foams, sprays, liquids, fogs and aerosols to enhance the rate of reactions leading to neutralization of chemical compounds, and other additives which serve to kill or attenuate certain biological compounds or agents.
Terrorist threats, potentially involving weapons of mass destruction, are increasing both in the United States and abroad. The use, and threat of use, of chemical and biological agents in the context of weapons of mass destruction are of paramount concern both to national defense as well as to state and local law enforcement.
Certain CW agents known to pose a threat by terrorists share chemical characteristics that present an opportunity for the development of countermeasures. The chemical agents sarin, soman, and tabun (G-agents) are all examples of phosphorus-containing compounds which, when altered chemically, can lose their toxicity. Mustard, which is an example of the H-agents, and VX, which is an example of the V-agents, can also be altered chemically and rendered harmless. In addition, certain of the known BW agents include botulinum toxin, anthrax and other spore-forming bacteria, vegetative bacteria, including plague and various viruses can also be deactivated chemically.
A CW or BW attack can involve either local placement or wide dispersal of the agent or agents so as to affect a population of human individuals. Because of the flexibility with which CW and BW (CBW) agents can be deployed, respondents might encounter the agents in a variety of physical states including bulk, aerosol and vapors.
An effective, rapid, and safe (non-toxic and non-corrosive) decontamination technology is required for the restoration of civilian facilities in the event of a domestic terrorist attack. Ideally, this technology should be applicable to a variety of scenarios such as the decontamination of open, semi-enclosed, and enclosed facilities as well as sensitive equipment. Examples of types of facilities where the decontamination formulation may be utilized include a stadium (open), an underground subway station (semi-enclosed), and an airport terminal or office building (enclosed).
Decontamination of chemical compounds have focused primarily on chemical warfare agents, particularly on the nerve agents (such as G agents and V agents) and on the blistering agents (such as mustard gas, or simply, mustard). Reactions involved in detoxification of chemical agents can be divided into substitution and oxidation reactions. Decontamination of biological agents is primarily focused on bacterial spores (e.g., anthrax) which are considered to be the most difficult of all microorganisms to kill.
Substitution Reactions
Hydrolysis of chemical agents can be carried out with water, hydroxyl ions or other nucleophiles. The rate of hydrolysis of mustard and the nature of the products formed depends primarily on the solubility of the agent in water and on the pH of the solution. In the detoxification of mustard, for example, the molecule first forms a cyclic sulfonium cation, which reacts with nucleophilic reagents (Yang, 1995). The dominant product is thiodiglycol but this product may react with sulfonium ions to give secondary intermediates.
The hydrolysis of sarin (GB) and soman (GD) occurs rapidly under alkaline conditions and gives the corresponding O-alkyl methylphosphonic acid. In contrast, the hydrolysis of VX with OHxe2x88x92 ions is more complex. In addition to displacement of the thioalkyl group (i.e., Pxe2x80x94S bond breakage), the O-ethyl group is displaced (i.e., Pxe2x80x94O bond breakage) producing a toxic product known as EA-2192 (Yang et al., 1997). Nucleophiles enter and depart the intermediate from an apical position. Electronegative groups, such as RO groups, preferentially occupy apical positions and groups that are bulky or electron donors, such as RS groups, occupy equatorial positions. The final product will depend on the balance between apicophilicity and leaving group ability. The result is that Pxe2x80x94S bond cleavage is favored over Pxe2x80x94O bond cleavage by a factor of about 5. Peroxyhydrolysis, on the other hand, using OOHxe2x88x92 ions in alkaline medium was shown to involve quantitative Pxe2x80x94S cleavage at rates 30-40 times that with OHxe2x88x92. This selectivity was related to the relative basicities of the anionic nucleophile and the leaving anions.
Catalytic species for acceleration of substitution reactions have been reported. One example is o-iodosobenzoate (IBA). An example illustrating the catalytic reactions of this compound is given by Moss and Zhang (1993). In this example, IBA is converted to iodoxybenzoate (IBX) via oxidation that then participates in the reaction with the CW agent.
The IBA compound was also functionalized to introduce surface activity (surfactant character) to the active group (Moss et al., 1986). Metal ion-amine complexes, with surface active moiety, were also developed and shown to exhibit catalytic effects in substitution reactions. Enzymes such as organophosphorous acid anhydrolase have also been shown to accelerate substitution reactions with the G and VX agents.
Oxidation Reaction
Oxidative decontamination methods are useful for mustard and VX (Yang, 1995). An early oxidant used was potassium permanganate. Recently, a mixture of KHSO5, KHSO4, and K2SO4 was developed. Several peroxygen compounds have also been shown to oxidize chemical agents (e.g., perborate, peracetic acid, m-chloroperoxybenzoic acid, magnesium monoperoxyphthalate, and benzoyl peroxide). More recently, hydroperoxycarbonate anions produced by the reaction of bicarbonate ions with hydrogen peroxide have been shown to effectively oxidize mustard and VX. Polyoxymetalates are being developed as room temperature catalysts for oxidation of chemical agents but the reaction rates are reported to be slow at this stage of development. Some of these compounds undergo a color change upon interaction with chemical agents to indicate the presence of chemical agents.
The BW threat can be more serious than the CW threat. This is in part because of the high toxicity of BW agents, their ease of acquisition and production, and difficulty in detection. There are hundreds of biological warfare agents available for use by terrorists. They may be grouped into the categories of spore forming bacterium (e.g., anthrax), vegetative bacterium (e.g., plague, cholera), virus (e.g., smallpox, yellow fever), and bacterial toxins (e.g., botulism, ricin). Bacterial spores are recognized to be the most difficult microorganism to kill.
Bacterial spores are highly resistant structures formed by certain gram-positive bacteria usually in response to stresses in their environment. The most important spore-formers are members of the genera, Bacillus and Clostridium. Spores are considerably more complex than vegetative cells. The outer surface of a spore consists of the spore coat that is typically made up of a dense layer of insoluble proteins usually containing a large number of disulfide bonds. The cortex consists of peptidoglycan, a polymer primarily made up of highly crosslinked N-acetylglucosamine and N-acetylmuramic acid. The spore core contains normal (vegetative) cell structures such as ribosomes and a nucleoid.
Since their discovery, considerable research has been carried out to investigate methods to kill bacterial spores. Although spores are highly resistant to many common physical and chemical agents, a few antibacterial agents are also sporicidal. However, many powerful bactericides may only be inhibitory to spore germination or outgrowth (i.e., sporistatic) rather than sporicidal. Examples of sporicidal reagents, using relatively high concentrations, include glutaraldehyde, formaldehyde, iodine and chlorine oxyacids compounds, peroxy acids, and ethylene oxide. In general, all of these compounds are considered to be toxic.
There are several mechanisms generally recognized for spore kill. These mechanisms can operate singularly or simultaneously. In one mechanism, the dissolution or chemical disruption of the outer spore coat can allow penetration of oxidants into the interior of the spore. Several studies (King and Gould, 1969; Gould et al., 1970) suggest that the Sxe2x80x94S (disulfide) rich spore coat protein forms a structure which successfully masks oxidant-reactive sites. Reagents that disrupt hydrogen and Sxe2x80x94S bonds increase the sensitivity of spores to oxidants.
Peptidoglycan, which is loosely cross-linked and electronegative, makes up the cortex of a spore. In another mechanism, cationic interaction between a disinfectant solution and peptidoglycan can cause collapse of the cortex and loss of resistance.
The peptidoglycan of spore-forming bacteria contains teichoic acids (i.e., polymers of glycerol or ribitol joined by phosphate groups). In another mechanism, disruption of the teichoic acid polymers can cause deficiencies in the peptidoglycan structure making the spore susceptible to attack.
Additionally, certain surfactants can increase the wetting potential of the spore coat to such an extent as to allow greater penetration of oxidants into the interior of the spore.
There are a variety of materials that can be used to address the decontamination of one or more CW or BW agents. Historically, decontamination solutions have focused strictly on the kill and neutralization of chemical and biological agents. Little emphasis has been placed on restoration and re-use of facilities and equipment. Instead, these items were considered to be expendable and were expected to be replaced in the event of a CBW (both CW and BW) attack. Thus, most decontamination formulations currently in use are both highly toxic and highly corrosive. Additionally, most of the materials used for decontamination address either CW or BW but not both and often only a subclass of either CW or BW agents.
The neutralization of chemical warfare agents began by using bleaching powder to neutralize mustard agent. Supertropical bleach, a mixture of 93% calcium hypochlorite and 7% sodium hydroxide, was then formulated and is more stable than bleach in long-term storage and easier to spread. Mustard gas reacts with bleach by oxidation of the sulfide to sulfoxide and sulfone and by dehydrochlorination to form compounds such as O2S(CHCH2)2. The G agents are converted by hydrolysis to the corresponding phosphonic acids with the hypochlorite anion acting as a catalyst. In acidic solutions, VX is oxidized rapidly by bleach at the sulfur atom and dissolves by protonation at the nitrogen. On the other hand, at high pH, the solubility of VX is significantly reduced and the deprotonated nitrogen is oxidized leading to consumption of greater than stoichiometric amounts of bleach.
A non-aqueous liquid composed of 70% diethylenetriamine, 28% ethylene glycol monomethyl ether, and 2% sodium hydroxide, referred to as Decontamination Solution Number 2 (DS2), is a highly effective decontaminant for CW agents. Ethylene glycol monomethyl ether has shown tetragonicity in mice and replacement with propylene glycol monomethyl ether was proposed to produce a new formulation referred to as DS2P. In addition, DS2 attacks paints, plastics, and leather materials. To minimize these problems, the contact time with DS2 is generally limited to 30 minutes followed by rinsing with large amounts of water. Personnel handling DS2 are required to wear respirators with eye shields and chemically protective gloves. The reactions of DS2 with mustard lead to elimination of HCl. The nerve agents react with DS2 to form diesters, which further decompose to the corresponding phosphonic acid. DS2 is not very effective in killing spores. Only 1-log kill (90%) was observed for Bacillus subtilis after 1 hour of treatment (Tucker, 2000).
A mixture consisting of 76% water, 15% tetrachloroethylene, 8% calcium hypochlorite, and 1% anionic surfactant mix was shown to enhance the solubility of agents but contains toxic and corrosive material (Ford and Newton, 1989). It is also not stable towards segregation.
There are a variety of formulations that are currently used for the decontamination of personnel in the event of a CW agent attack, primarily used by the U.S. military and are, in general, not utilized in the civilian community. One formulation is a M258 skin decontamination kit that mimics a Soviet kit recovered in Egyptian tanks in the Yom Kippur war. The kit consists of two packets: Packet I contains a towelette prewetted with phenol, ethanol, sodium hydroxide, ammonia, and water. Packet II contains a towelette impregnated with chloramine-B and a sealed glass ampoule filled with zinc chloride solution. The ampoule in packet II is broken and the towelette is wetted with the solution immediately prior to use. The presence of zinc chloride maintains the pH of the chloramine-B in water between 5 and 6 which would otherwise rise to 9.5.
Another formulation is the M291 kit, which is a solid sorbent system (Yang, 1995). The kit is used to wipe bulk liquid agent from the skin and is composed of non-woven fiber pads filled with a resin mixture. The resin is made of a sorptive material based on styrene/divinylbenzene and a high surface area carbonized macroreticular styrene/divinylbenzene resin, cation-exchange sites (sulfonic acid groups), and anion-exchange sites (tetraalkylammonium hydroxide groups). The sorptive resin can absorb liquid agents and the reactive resins are intended to promote hydrolysis of the reactions. However, a recent NMR study has shown neither VX nor a mustard simulant were hydrolyzed on the XE-555 resin surface during the first 10 days (Leslie et al., 1991). GD slowly hydrolyzed with a half-life of about 30 hours. The observed rapid agent decontamination in the field is achieved physically by wiping. This resin blend was found to be less corrosive to the skin than the M258 system.
Most formulations used for the decontamination of BW agents by both military and civilian agencies contain the hypochlorite anion (i.e., bleach or chlorine-based solutions). Solutions containing concentrations of 5% or more bleach have been shown to kill spores (Sapripanti and Bonifacino, 1996). A variety of hypochlorite solutions have been developed for decontamination of BW agents including 2-6 percent aqueous sodium hypochlorite solution (household bleach), a 7 percent aqueous slurry or solid calcium hypochlorite (HTH), 7 to 70 percent aqueous slurries of calcium hypochlorite and calcium oxide (supertropical bleach, STB), a solid mixture of calcium hypochlorite and magnesium oxide, a 0.5 percent aqueous calcium hypochlorite buffered with sodium dihydrogen phosphate and detergent, and a 0.5 percent aqueous calcium hypochlorite buffered with sodium. Although all of these solutions, with varying efficiency, are capable of killing spores, each is also highly corrosive to equipment and toxic to personnel.
The compounds that have been developed for use in detoxification of both CW and BW agents have been deployed in a variety of ways, including liquids, foams, fogs and aerosols). Stable aqueous foams have been used in various applications including fire fighting and law enforcement applications (such as prison riot containment). Such foams, however, have typically been made using anionic surfactants and anionic or nonionic polymers. These foams, unfortunately, have not been effective in the chemical decomposition and neutralization of most chemical and biological weapons (CBW) agents. They did not have the necessary chemical capabilities to decompose or alter CW agents, and they are not effective in killing or neutralizing the bacteria, viruses and spores associated with some of the more prevalent BW agents.
Gas phase reagents are attractive for decontamination if an environmentally acceptable gas can be identified. The advantage of gas decontaminants is their penetrating (diffusing) capability that makes them a necessary complement to the other decontamination techniques. Ozone, chlorine dioxide, ethylene oxide, and paraformaldehyde have all been investigated for decontamination applications. These are all known to be effective against biological agents. The effectiveness of ozone for killing spores appears to be well established (Raber et al., 1998). While ozone is an attractive decontaminant, experiments by Edgewood Chemical Biological Center (ECBC) show that it is not effective towards GD and with VX it leads to the formation of toxic products via Pxe2x80x94O bond cleavage (Hovanic, 1998).
Useful would be materials that are effective for neutralizing both chemical and biological agents, that are environmentally benign to both people and property, that work on all currently anticipated material surfaces, and that can be incorporated into a wide variety of carriers (foams, gels, fogs, aerosols) that satisfy a wide variety of operational objectives.